TasA-tasB, a new putative toxin-antitoxin (TA) system from Bacillus thuringiensis pGII plasmid is a widely distributed composite mazE-doc TA system

Background: Post-segregational killing systems are present in a large variety of microorganisms. When found on plasmids, they are described as addiction systems that act to maintain the plasmid during the partitioning of the cell. The plasmid to be maintained through the generations harbours a group of two genes, one coding for a stable toxin and the other coding for an unstable antitoxin that inhibits the effects of the toxin. If, during cell division, the plasmid is lost, the toxin and antitoxin proteins present in the cytosol cease to be newly expressed. The level of unstable antitoxin protein then rapidly decreases, leaving the toxin free to act on the cellular target, leading to cell death. Consequently, only cells harbouring the plasmid can survive. Results: The pGII plasmid of Bacillus thuringiensis H1.1 harbours a group of two genes, one showing similarities with the Doc toxin of the phd-doc toxin-antitoxin system, potentially coding for a toxin-antitoxin system. Attempts were made to clone this putative system in the Gram-negative host Escherichia coli. The putative antitoxin tasA was easily cloned in E. coli. However, although several combinations of DNA fragment were used in the cloning strategy, only clones containing a mutation in the toxin gene could be recovered, suggesting a toxic activity of TasB. An exhaustive search was carried out in order to index genes homologous to those of the putative tasA-tasB system among microorganisms. This study revealed the presence of this system in great number and in a large variety of microorganisms, either as tasA-tasB homologues or in association with toxins (or antitoxins) from other TA systems. Conclusion: In this work, we showed that the pGII plasmid of B. thuringiensis H1.1 harbours genes resembling a toxin-antitoxin system, named tasA-tasB for thuringiensis addiction system. This system appeared to be functional but unregulated in E. coli. Bioinformatics studies showed that the tasAB system is present on plasmids or chromosomes of a large variety of microorganisms. Moreover, the association between TasA antitoxin with toxins other than TasB (and vice versa) revealed the composite and modular nature of bacterial TA systems.